Potassium Carbonate → Tert-butyl 6-(1-methyl-1,2,3,4-tetrahydroquinoxalin-6-yl)picolinate

HRID 2178239Notes

Reaction equation

HRID 2178239 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:5]=[CH:4][CH:3]=1.[CH3:15][N:16]1[C:25]2[C:20](=[CH:21][C:22](B3OC(C)(C)C(C)(C)O3)=[CH:23][CH:24]=2)[NH:19][CH2:18][CH2:17]1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:15][N:16]1[C:25]2[C:20](=[CH:21][C:22]([C:2]3[N:7]=[C:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:5]=[CH:4][CH:3]=3)=[CH:23][CH:24]=2)[NH:19][CH2:18][CH2:17]1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 23432991tert-Butyl 6-bromopicolinateHCID 594187141-Methyl-1,2,3,4-tetrahydroquinoxaline-6-boronic Acid Pinacol Ester

Product 1

HCID 59418755Tert-butyl 6-(1-methyl-1,2,3,4-tetrahydroquinoxalin-6-yl)picolinateYield 38.3%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

Tert-butyl 6-bromopicolinate (25A) (157 mg, 0.61 mmol) in 1,4-dioxane (1.0 mL) was added dropwise to 1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinoxaline (25F) (167 mg, 0.61 mmol), K2CO3 (207 mg, 1.52 mmol), tetrabutylammonium bromide (19.5 mg, 0.061 mmol), and dichlorobis(triphenylphosphine)palladium(II) (17.9 mg, 0.024 mmol) in 1,4-dioxane (2.0 mL) and water (1.0 mL) at rt. The mixture was microwave (150 W) heated to 100° C. for 50 minutes, cooled to 20° C., diluted with water and extracted with EtOAc. The organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash column chromatography on silica gel eluting with a gradient of PE:EtOAc 100:0-70:30, to provide 76 mg (38%) of the desired product tert-butyl 6-(1-methyl-1,2,3,4-tetrahydroquinoxalin-6-yl)picolinate (25G): 1H NMR (300 MHz, MeOD) δ 7.84-7.78 (3H, m), 7.35 (1H, d), 7.30 (1H, d), 6.62 (1H, d), 3.41 (2H, t), 3.31 (2H, t), 2.92 (3H, bs), 1.64 (9H, s).

Workup

  1. temperaturecooled to 20° C.
  2. extractionextracted with EtOAc
  3. washThe organic phases were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by flash column chromatography on silica gel eluting with a gradient of PE

Sources & evidence

ORD record
ord-156d816c35a04e088c75abeaa811ff77
Source dataset
uspto-grants-2015_06
Patent number
US09067928B2

Reaction notes

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